Aluminium dodecatungstophosphate (AlPW12O40)-An efficient catalyst for three-component Mannich reaction in water

Article abstract of DOI:10.1134/S0023158411040045

One-pot, three-component Mannich reactions of ketones, aldehydes and amines were efficiently catalyzed by AlPW₁₂O₄₀ in water at ambient temperature to give the corresponding β-amino ketones in good to excellent yields. The method has the following merits: Firstly, Catalyst AlPW₁₂O₄₀ is non-corrosive and environmentally benign; Secondly, loading amount of catalyst is very low, less than 1 mol %; Thirdly, water as solvent is green and safe.

Full text of DOI:10.1134/S0023158411040045

ISSN 0023ꢀ1584, Kinetics and Catalysis, 2011, Vol. 52, No. 4, pp. 559–563. © Pleiades Publishing, Ltd., 2011.
Published in Russian in Kinetika i Kataliz, 2011, Vol. 52, No. 4, pp. 569–573.
Aluminium Dodecatungstophosphate (AlPW12O40)—An Efficient
Catalyst for ThreeꢀComponent Mannich
Reaction in Water1
Li Ganga, Long Ruilingb, Yang Sulinga, and Zhang Lipinga
a College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang 455002, People’s Republic of China
b Department of Life Science and Technology, Xinxiang Medical University, Xixiang 453000, People’s Republic of China
eꢀmail: lgorgchem@126.com
Received September 16, 2010
Abstract—Oneꢀpot, threeꢀcomponent Mannich reactions of ketones, aldehydes and amines were efficiently
catalyzed by AlPW12O40 in water at ambient temperature to give the corresponding ꢀamino ketones in good
β
to excellent yields. The method has the following merits: Firstly, Catalyst AlPW12O40 is nonꢀcorrosive and
environmentally benign; Secondly, loading amount of catalyst is very low, less than 1 mol %; Thirdly, water
as solvent is green and safe.
DOI: 10.1134/S0023158411040045
1
Organic reactions in water are a hot study field in reported in open literatures [6–9]. Various catalysts
including Lewis acids [10], Lewis bases [11], Brønsted
acids [12, 13], rare metal salts [14], and organic small
molecules have been used to promote the Mannich
reaction [15]. However, most of these are plagued by
several evident drawbacks, for example toxicity, corroꢀ
sivity, expensive catalysts or using organic solvents.
Hence, there is high interest in pursuing an efficient,
green method for Mannich reaction.
Heteropoly acids and its salts as highly active and
environmentally benign solid acids have been used to
catalyze many organic reations such as esterifications
[16–18], Friedel–Crafts [19, 20] and Diels–Alder
reactions [21]. Mannich reaction catalyzed by hetꢀ
recent years because water used as reaction medium
has several advantages [1–3]. Firstly, in comparison
with organic solvent often used in organic chemical
reaction, water is a green and safe solvent. Risk in proꢀ
duction process greatly decreases; Secondly, water’s
unique physical and chemical properties lead to
unique reactivity and selectivity of organic reaction in
water, which cannot be attained in organic solvents;
Thirdly, water is cheap and organic reactions in water
do not require to use expensive anhydrous reactants
and reagents. So, the cost of product evidently
decreases. Finally, the operation after reaction is simꢀ
ple. The organic product which is insoluble in water
can be separated from water by simple filtration or sepꢀ eropoly acids have been also covered in several literaꢀ
aratory funnel.
tures [22–24]. AlPW12O40 as a water stable, highly
active nonꢀcorrosive and environmentally benign salt
have been used to catalyze several organic reactions
[25–27], while Mannich reaction catalyzed by
AlPW12O40 is not reported in open literatures so far. In
this paper, we describe that oneꢀpot threeꢀcomponent
Mannich reactions of ketones, aldehydes and amines in
water at room temperature were efficiently catalyzed by
Mannich reaction is one of the most important
multicomponent carbon–carbon bondꢀforming reacꢀ
tions in organic synthesis and one of the most fundaꢀ
mental and classical routes to prepare ( ꢀamino
β
ketones and their derivatives, which are versatile synꢀ
thetic intermediates for various pharmaceuticals, natꢀ
ural products and biologically active compounds [4, 5].
The ubiquitous nature of nitrogenꢀcontaining comꢀ
pounds including proteins, nucleic acids and most
biologically active compounds arouses an increasing
interest in Mannich reaction. Mannich reaction can
happen using either twoꢀcomponent system or threeꢀ
component system. However, the preferable route is
oneꢀpot threeꢀcomponent Mannich reaction of
ketone, aldehyde, and amine. Up to now, many protoꢀ
cols for threeꢀcomponent Mannich reaction have been
AlPW12O40 to give the corresponding ꢀamino ketones
in good to excellent yields.
β
EXPERIMENTAL
Materials and Methods
All the chemicals and reagents used were of analytꢀ
ical grade and were used without further purification.
The structure and syn/anti ratio of products were
determined by IR, 1H NMR. IR spectra were recorded
on a Bruker AMꢀ400 spectrometer using KBr discs.
1
The article is published in the original.
559

560
LI GANG et al.
Table 1. Direct threeꢀcomponent Mannich reaction catalyzed by different metal salts in water
Ph
Ph
O
O
HN
0.5 mol % AlPW12O40
3 mL H O, rt
Ph
CHO + Ph NH2 +
2
Ph
Me
Ph
10 mmol
10 mmol
10 mmol
Entry
Catalyst
Amount of Cat, mol %
Time, h
Yield, %
1
2
3
4
5
6
7
8
9
AlCl3
Al2(SO4)3
10
10
5
24
24
24
24
16
24
24
24
24
0
0
Al(SO3CH3)3
Al(SO3C6H4CH3ꢀ
24
63
93
0
p)
5
3
AlPW12O40
Na3PW12O40
0.5
2
Mg3(PW12O40)2
Zn3(PW12O40)2
LnPW12O40
5
21
72
86
5
5
1H NMR spectra were obtained from solution in Al(SO3C6H4CH3ꢀp 3
)
could catalyze Mannich reaction
under the same condition (entries 3, 4), but they were
much inferior to AlPW12O40. Other phosphotungstate
salts were also used to catalyze the model Mannich
reaction under the same condition, activity of
Mg3(PW12O40)2 and Na3PW12O40 were very low, even
nought (entries 6, 7). Zn3(PW12O40)2 and LnPW12O40
could smoothly catalyze Mannich reaction in water
(entries 8, 9), but their activities were lower than that
of AlPW12O40. These results demonstrated that both
3−
CDCl3 with TMS as internal standard using a Varian
Scimitar Series 800 (400 MHz) spectrometer. Melting
points were determined in open capillaries.
General Procedure for Mannich Reaction Catalyzed
by AlPW12O40 in Water
Aldehyde (10 mmol), amine (10 mmol) and ketone
(10 mmol) were added to a solution of AlPW12O40 in
water (3 mL) placed in a 50 mL oneꢀnecked roundꢀ
bottom flask. Then, the reaction mixture was stirred
(500 rts/min) vigorously with a magnetic stirrer at
ambient temperature for the mentioned time. After
reaction completion, the crude mixture was either
purified by silica gel chromatography (ethyl aceꢀ
tate/petroleum ether mixtures) or recrystallization
from ethanol or ethanolꢀacetone (v/v = 1 : 1) to afford
the corresponding compound.
cation Al3+ as a benign Lewis acid and
felicitous anion were integrant factors to catalyze effiꢀ
ciently threeꢀcomponent Mannich reaction in water.
as a
PW12O40
AlPW12O40ꢀCatalyzed Mannich Reaction
of Aromatic Ketones
Encouraged by the remarkable results, we explored
the generality and scope of AlPW12O40ꢀcatalyzed oneꢀ
pot threeꢀcomponent Mannich reaction in water, the
reaction was examined with various structurally
ketones, aldehydes and amines under the same condiꢀ
tion.
RESULTS AND DISCUSSION
Catalytic Activities of Various Metal Salts
in Esterification
The Mannich reaction of aromatic ketones with
various aromatic aldehydes and amines could be cataꢀ
lyzed by AlPW12O40 in water in good to excellent yields
as shown in Table 2. These results revealed the followꢀ
ing characters:
Initially, we selected Mannich reaction of an
equimolar amount of benzaldehyde, aniline, and aceꢀ
tophenone as a model reaction to screen catalysis
activities of various usual metal salts for oneꢀpot threeꢀ
component Mannich reaction in water at room temꢀ
perature. As shown in Table 1, among these catalysts
used, AlPW12O40 was the most efficient catalyst for the
(1) When anisaldehyde bearing strong electronꢀ
donating methoxy group was used as reaction subꢀ
Mannich reaction in water at ambient temperature. strate, yield was distinctly low because electronꢀ
Only 0.5 mol % of AlPW12O40 was enough to efficiently donating action of methoxy group decrease electroꢀ
philicity of carbonyl carbon atom (entries 2, 7);
catalyze Mannich reaction in an excellent yield 93%
(entry 5). Comparatively, other aluminum salts (AlCl3
and Al2(SO4)3) had not catalysis towards Mannich
reaction in water (entries 1, 2). Al(SO3CH3)3 and
(2) It is worthly to say that an excellent yield could
also be obtained for reaction of 3ꢀnitroaniline with
strong electronꢀwithdrawing nitro group (entries 4, 9);
KINETICS AND CATALYSIS Vol. 52
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ALUMINIUM DODECATUNGSTOPHOSPHATE
561
Table 2. AlPW12O40ꢀcatalyzed threeꢀcomponent Mannich reaction of Aromatic Ketones in Water
Ar3
O
O
HN
0.5 mol % AlPW12O40
+ Ar2
CHO + Ar3 NH2
3 mL H O, rt
2
Ar1
10 mmol
CH3
Ar1
Ar2
10 mmol 10 mmol
Yield, % a
T. mp., °C
Entry
1
Aldehyde
Amine
NH2
Ketone
Time, h
18
O
95
54
93
167–168
148–150
161–162
CHO
CH3
O
2
3
20
16
CH3O
CHO
NH2
CH3
O
CHO
CHO
CH3
NH2
CH3
O
NH2
4
16
94
144–146
CH3
NO2
O
5
6
7
8
20
20
18
15
74
80
48
90
148–150
128–130
142–143
150–151
CHO
CHO
CH3O
NH2
CH3
O
H3C
H3C
H3C
NH2
NH2
CH3
O
CH3O
CHO
CH3
O
CHO
CHO
CHO
CH3
NH2
CH3
O
NH2
H3C
H3C
9
15
21
83
45
130–132
128–130
CH3
NO2
O
10
CH3O
NH2
CH3
a
Note: isolated yields (data were obtained according to amount of product purified by gel chromatography or recrystallization).
KINETICS AND CATALYSIS Vol. 52 No. 4 2011

562
LI GANG et al.
Table 3. AlPW12O40ꢀcatalyzed threeꢀcomponent Mannich reaction of Aliphatic Ketones in Water
O
O
Ar1
O
Ar2
0.15 mol % AlPW12O40
N
H
3 mL H O, rt
2
Ar1
CHO + Ar2
+
NH2
Ar1
O
0.3 mol % AlPW12O40
Ar2
3 mL H O, rt
2
N
H
10 mmol
Aldehyde
10 mmol
Amine
10 mmol
Yield, % a
95
syn
/
antib
Entry
1
Ketone Time, h
T. mp., °C
O
1
48/52
49/51
39/61
47/53
50/50
136–138
131–133
138–140
116–117
139–140
CHO
NH2
NH2
O
2
3
4
5
15
75
92
91
94
CH3O
CHO
O
4
CHO
CHO
Cl
NH2
O
8
CH3
Cl
NH3
O
8
Cl
CHO
NH2
O
6
7
8
15
76
82
91
62
53/47
53/47
52/48
51/49
123–125
103–105
138–140
CHO
CHO
CHO
NH2
O
18
CH3
Cl
NH3
O
10
NH2
O
9
18
120–122
Cl
CHO
Cl
NH2
a
b
Note: isolated yields (data were obtained according to amount of product purified by gel chromatography or recrystallization), anti/syn
1
ratio was determined by H NMR spectroscopy analysis of the crude reaction mixture.
KINETICS AND CATALYSIS Vol. 52
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2011

ALUMINIUM DODECATUNGSTOPHOSPHATE
563
6. Zhao, G., Jiang, T., Gao, H., Han, B., Huang, J., and
Sun, D., Green. Chem., 2004, vol. 6, p. 75.
7. Guo, Q.X., Liu, H., Guo, C., Luo, S.W., Gu, Y., and
(3) In general, the reactivity of pꢀmethylacetopheꢀ
none was a little lower than that of acetophenone.
Gong, L.Z., J. Am. Chem. Soc., 2007, vol. 129, p. 3790.
8. Wang, S., Matsumura, S., and Toshima, K., Tetraheꢀ
dron Lett., 2007, vol. 48, p. 6449.
AlPW12O40ꢀCatalyzed Mannich Reaction
of Aliphatic Ketones
Furthermore, we used AlPW12O40 to catalyze Manꢀ
nich reaction of aliphatic ketones such as cyclohexꢀ
anone and 3ꢀpentanone, as substrate in water. It can be
seen from Table 3 that reactivities of aliphatic ketones
were obviously superior to those of aromatic ketones.
Smaller amount of AlPW12O40 could efficiently cataꢀ
lyze Mannich reaction of aliphatic ketones. Especially,
9. Reddy, B.M., Pati, M.K., and Reddy, B.T., Catal. Lett.
2008, vol. 125, p. 97.
10. Li, H., Zeng, H.Y., and Shao, H.W., Tetrahedron Lett.
,
,
2009, vol. 50, p. 6858.
11. Wu, H., Chen, X.M., Wan, Y., Ye, L., Xin, H.Q.,
Xu, H.H., Yue, C.H., Pang, L.L., Ma, R., and
Shi, D.Q., Tetrahedron Lett., 2009, vol. 50, p. 1062.
Mannich reaction of cyclohexanone, benzaldehyde 12. Hashem, S. and Mahboubeh, J., Can. J. Chem., 2010,
vol. 88, p. 14.
and aniline, not only was amount of catalyst
AlPW12O40 used less, but also reaction rate was very
quick. An excellent yield 95% could be obtained in
13. Dagousset, G., Drouet, F., Masson, G., and Zhu, J.P.,
Org. Lett., 2009, vol. 11, p. 5546.
one hour in the present of only 0.15 mol % AlPW12O40
.
14. Wang, L.M., Han, J.W., Sheng, J., Tian, H., and
Fan, Z.Y., Catal. Commun., 2005, vol. 6, p. 201.
15. List, B., Pojarliev, P., Biller, W.T., and Martin, H.J.,
J. Am. Chem. Soc., 2002, vol. 124, p. 827.
16. Cardoso, A., Augusti, L., Da, R., and Silva, M.J., J.Am.
Oil Chem. Soc., 2008, vol. 85, p. 555.
In conclusion, AlPW12O40 could highly efficiently
catalyze oneꢀpot threeꢀcomponent Mannich reaction
of an equal mole amount of aldehydes, amines and
ketones at ambient temperature to obtain
βꢀamino
ketones. The method exhibits several merits: Firstly, as
compared with heteropoly acids, AlPW12O40 as a water 17. Joshaghani, M., Tork, F., Fakhri, A., and Eavani, S.,
J. Mol. Catal. A: Chem., 2008, vol. 283, p. 1.
18. Engin, A., Haluk, H., and Gurkan, K., Green Chem.
2003, vol. 5, p. 460.
19. Kaur, J., Griffin, K., Harrison, B., and Kozhevnikov, I.V.,
stable salt is nonꢀcorrosive and environmentally
benign; Secondly, loading amount of catalyst green is
very low, less than 1 mol %; Thirdly, water as solvent is
green and safe. So, it was an attractive and promising
,
J. Catal., 2002, vol. 208, p. 448.
method to synthesize
β
ꢀamino ketones in laboratory
and chemical industry.
20. Kaur, J., Kozhevnikova, E.F., Griffin, K., Harrison, B.,
and Kozhevnikov, I.V., Kinet. Catal., 2003, vol. 44,
p. 175.
ACKNOWLEDGMENTS
21. Meuzelaar, G.J., Maat, L., Sheldon, R.A., and
Kozhevnikov, I.V., Catal. Lett., 1997, vol. 45, p. 249.
22. Azizi, N., Torkiyan, L., and Mohammad, R.S., Org.
Lett., 2006, vol. 8, p. 2079.
The authors thank Nature Science Foundation of
Anyang Normal University for financial support.
23. Rasalkar, M.S., Bhilare, S.V., Deorukhkar, A.R., Darꢀ
REFERENCES
vatkar, N.B., and Salunkhe, M.M., Can. J. Chem.
2007, vol. 85, p. 77.
,
1. Chanda, A. and Valery, V.F., Chem. Rev., 2009, vol. 109,
pp. 725–748.
24. Wang, R., Huang, T., Shi, L., Li, B., and Lu, X.X., Synꢀ
lett, 2007, vol. 14, p. 2197.
25. Firouzabadi, H., Iranpoor, N., Nowrouzi, F., and
2. Li, C.J. and Chang, T.H., Organic Reactions in Aqueous
Media, New York: Wiley, 1997.
Amani, K., Chem. Commun., 2003, vol. 6, p. 764.
26. Firouzabadi, H., Iranpoor, N., Nowrouzi, F., and
3. Grieco, P.A., Organic Synthesis in Water, London:
Blacky Academic and Professional, 1998.
4. Arend, M., Westermann, B., and Risch, N., Angew.
Chem. Int. Ed., 1998, vol. 37, p. 1044.
5. Cordova, A., Acc. Chem. Res., 2004, vol. 37, p. 102.
Aman, I.K., Tetrahedron Lett., 2003, vol. 44, p. 3951.
27. Firouzabadi, H., Iranpoor, N., and Jafari, A.A., J. Mol.
Catal. A: Chem., 2005, vol. 227, p. 97.
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2011